Know Your Naloxone: Save a Life
Medically reviewed on Apr 5, 2018 by L. Anderson, PharmD.
The Opioid Overdose Reality
On average, 115 Americans die every day from an opioid overdose. That's one person every 12.5 minutes.
In the US, the death rate from prescription opioid overdoses has increased 4-fold since 1999, while deaths from heroin deaths have more than quadrupled since 2010. From 2000 to 2016, over 600,000 people died from drug overdoses. In 2016 alone, more than 63,600 drug overdose deaths occurred in the U.S., based on a report from the CDC released in December 2017.
Opioids are a class of drugs that include narcotic analgesic prescription medications such as:
- oxycodone (Oxycontin)
- hydrocodone (Hysingla ER, Zohydro ER)
- acetaminophen and hydrocodone (Vicodin. Lortab, Norco)
- fentanyl (Actiq, Durgesic, Lazanda)
Opioids also include heroin, an illicit and highly addictive drug.
In response, several state and federal initiatives are underway to combat this epidemic, and $3.2 billion in federal money was allocated in 2018 for this fight. Even the U.S. Surgeon General in April 2018 urged Americans to have naloxone on hand for emergency situations.
The FDA has also approved new naloxone agents that can reverse the depressed, often fatal slowed breathing (respiratory depression) that can occur with a narcotic overdose. These agents can be easily administered by emergency personel, families, friends or even bystanders to anyone experiencing an opioid overdose.
But until recently, naloxone agents weren't easily accessible by the public. Now they are, in most states.
How Do I Recognize an Opioid Overdose?
All opioids (narcotics) will produce various levels of central nervous system (CNS) depression and side effects such as drowsiness, sedation, and slowed breathing. In an overdose, you might notice stupor, coma, slurred speech, clammy skin, pinpoint pupils, and low blood pressure.
The most dangerous and often fatal side effect of an opioid overdose is respiratory depression - slowed or arrested breathing. This risk is multiplied when the narcotic is combined with alcohol or other CNS depressants.
If you believe someone has overdosed on narcotics, call 911 immediately. A reversal agent called naloxone can be life-saving for patients who overdose on narcotics, although in patients dependent upon opioids, it can also cause a severe withdrawal effect.
What is Naloxone?
Naloxone is a medication that rapidly reverses the effects of an opioid (narcotic) overdose and is the standard treatment.
Naloxone has been available in injection form to reverse the effects of opioid overdose for more than 40 years. It is not addictive or considered an opioid itself. Prior naloxone treatments required administration via a syringe and needle and were most commonly used by trained medical personnel and emergency responders.
In fact, most states have now passed legislation designed to improve lay-person naloxone access.
How Can Naloxone Save a Life?
Pharmacologically, naloxone is considered an opioid antagonist, meaning it blocks opioid receptors.
In fact, naloxone has no pharmacologic action in the absence of an actual opioid overdose. It is regularly used by first responders and can be administered by lay-people with little or no training.
Naloxone can counter overdose effects, including depressed breathing, drowsiness, and loss of consciousness - usually within 2 to 3 minutes - and can be given by family members or caregivers until emergency help arrives. In families or friends that elect to carry the devices or store these medications in their home, learning how to use them ahead of time may save time.
What Are Opioids?
Naloxone reverses the effects of prescription opioid overdoses, as well as heroin, but has no action in other types of overdoses such as benzodiazepines like alprazolam (Xanax) or lorazepam (Ativan), sedatives like barbiturates, or alcohol.
You should always call for emergency help when you use naloxone; you may not know what the person has overdosed on, or it may be a mixture of substances. Examples of prescription opioids that may be involved in an overdose include:
- buprenorphine (Buprenex)
- buprenorphine transdermal system (Butrans Skin Patch)
- codeine (Tylenol with Codeine #3, Tylenol with Codeine #4, Capital and Codeine Suspension)
- fentanyl (Abstral, Actiq, Duragesic, Fentora, Ionsys, Onsolis)
- hydrocodone (Hysingla ER, Zohydro ER, Vantrela ER)
- hydromorphone (Dilaudid; Dilaudid HP; Exalgo)
- meperidine (Demerol)
- methadone (Dolophine, Methadose)
- morphine (Kadian, MS Contin, MorphoBond, Arymo ER)
Narcan: The Original
The first FDA-approved naloxone was injectable Narcan which became available in the early 1970's.
The intravenous formulation is used in clinic and hospital settings, but an intramuscular formulation is available also, often sold in a kit with 2 syringes and 2 vials of 0.4 mg/mL naloxone and provided to emergency first-responders. The naloxone vials are also sold in a kit with nasal atomizers for use as a nasal spray. All kits contain an instruction chart for use and assembly direction.
Patients who cannot afford these medications, but need them, should call the US manufacturers (Kaleo for Evzio) or (Adapt Pharma for Narcan Nasal) to determine if they qualify for assistance, or if other pricing discounts or coupons are possible.
Evzio (naloxone hydrochloride) Autoinjector
In April 2014 the FDA approved Evzio (naloxone hydrochloride) as an emergency treatment for known or suspected opioid overdose.
Evzio delivers a single naloxone 0.4 mg dose via a hand-held auto-injector that can be carried in a pocket or stored in a medicine cabinet in a caregiver's home.
Another plus in an emergency situation -- when Evzio is turned on, it provides verbal instructions to the user. This is an obvious advantage in a stressful, emergency situation that a lay-person might encounter.
Because naloxone may not work as long as the opioid, a second repeat dose may be needed after 2 to 3 minutes until emergency help arrives.
How to Use Evzio Autoinjector
Read the "Instructions for Use" that comes with Evzio when you get it from the pharmacy or clinic. Evzio has built-in voice instructions to help guide administration, and directions are on the label, too.
When you need to use Evzio for an overdose:
- Pull Evzio from the outer case.
- Pull off the RED safety guard.
- Place the BLACK end of Evzio against the outer thigh. May administer through clothing if necessary.
- Press firmly and hold in place for 5 seconds.
- After using Evzio, get emergency medical help (call 911) right away. If symptoms return, another injection may be needed every 2 to 3 minutes.
- The Evzio Autoinjector cannot be reused; to re-administer another dose a new Evzio case must be activated.
Narcan Nasal Spray in Two Strengths
In November 2015 Narcan Nasal Spray 4 mg became available as the first FDA-approved nasal spray version of naloxone. A 2-mg strength was approved in Jan 2017. The 2-mg dose is for opioid-dependent patients expected to be at risk for severe opioid withdrawal in situations where there is a low risk for accidental or intentional opioid exposure by household contacts.
Narcan Nasal offers an advantage to the lay-person as, like Evzio, it is user-friendly and is easily carried in a purse or pocket or stored in the home.
In clinical studies, one dose of Narcan Nasal 4 mg resulted in similar levels to intramuscular (IM) injected naloxone 0.4 mg/mL and at roughly the same time.
How to Use Narcan Nasal Spray
Narcan Nasal Spray can be used for adults or children. The drug is sprayed into one nostril while the person is lying on their back. To use:
- Remove the Narcan Nasal Spray from box. DO NOT prime the device before administering. Place your thumb on the plunger bottom and your first and middle fingers on either side of nozzle.
- Tilt the person’s head back and provide neck support with your hand.
- Gently insert the nozzle tip in one nostril until your fingers on either side of the nozzle are against the bottom of the person’s nose. Press the plunger firmly to give the full dose.
- Get emergency medical help right away after giving the first dose of Narcan Nasal Spray. Rescue breathing or CPR may be given while waiting for emergency medical help.
- If symptoms return, give another dose in the other nostril after 2 to 3 minutes using a new Narcan Nasal Spray in alternate nostrils with each dose until emergency medical assistance arrives.
Fully review directions enclosed in the box when you receive the medication; do not wait until an emergent situation.
Naloxone Side Effects
Common naloxone side effects may include symptoms of opioid withdrawal such as:
- anxiety or agitation
- nausea or vomiting
- runny nose
- high blood pressure
Acute withdrawal from chronic opioid use may also result in seizures, pain, and elevated heart rate.
While naloxone will reverse some, but not all, symptoms caused by a tramadol (Ultram, ConZip) overdose, the risk of seizures is also increased with naloxone administration with tramadol, and may require treatment with an anti-seizure medication.
Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine (Buprenex) and pentazocine (Talwin) may be incomplete. Larger or repeat naloxone doses may be required.
Opioid Withdrawal Symptoms
In patients who are opioid-dependent, withdrawal symptoms can occur abruptly after administration of naloxone.
Sudden opioid withdrawal symptoms may include:
- Body aches, diarrhea, increased heart rate
- Fever, runny nose, sneezing
- Goose bumps
- Sweating, yawning, nausea or vomiting
- Nervousness, restlessness or irritability
- Shivering, trembling
- Stomach cramping, weakness, increased blood pressure
Who's At Risk?
It isn't surprising that many people involved in prescription and illegal drug misuse and overdose situations are hesitant to call for emergency help due to legal concerns.
However, many states have implemented "Good Samaritan" laws which allow first responders of any kind, including family and friends, to administer naloxone without prior approval from a doctor. Most states have passed legislation to improve layperson access to naloxone. The laws vary by state, particularly with regard to immunity from prosecution if found with possession of controlled substances.
An opioid prescribing guideline from the CDC and Surgeon General notes that healthcare providers should consider offering naloxone when prescribing opioids to patients at elevated overdose risk, including:
- patients with a history of overdose
- patients with a history of substance (opioid) use disorder; misusing prescription opioids (for example, oxycodone or hydrocodone); or heroin, fentanyl, or carfentanil
- patients taking benzodiazepines or alcohol with opioids
- patients at risk for returning to a high dose to which they are no longer tolerant (e.g., patients recently released from prison or being discharged from opioid detoxification that does not include ongoing use of methadone, buprenorphine, or naltrexone).
- patients taking higher dosages of prescription opioids (≥50 morphine milligram equivalents [MME] per day) for pain
Probuphine Implant: A New Option for Opioid Dependence
While Narcan can save a life from an overdose, a multi-pronged treatment plan is needed to rescue patients from chronic misuse of opioids.
As an added weapon in the treatment of opiate addiction, the FDA approved Probuphine in May 2016 as the first buprenorphine implant for the maintenance treatment of opioid dependence.
Probuphine consists of four, one-inch-long rods that are implanted under the skin and provide a constant, low-level dose of buprenorphine for six months.
In studies, 63 percent of Probuphine-treated patients had no evidence of illicit opioid use throughout the six months of treatment – similar to the 64 percent of those who responded to sublingual (under the tongue) buprenorphine alone.
The Path Forward in Saving Lives
Prescription drug addiction to opioids is a domestic threat unlike any other in the US. Concerted efforts from family, friends, health care providers, first-responders, and patients themselves are needed to combat this epidemic.
New, more user-friendly antidotes to reverse an opioid overdose are available, but accessibility for all parties is needed. Patients and caregivers should discuss whether or not the quick availability of a naloxone product makes sense in their situation.
Individual medical advice should always come from your healthcare provider, but to keep up-to-date with the latest news, or to voice questions or concerns, consider joining the Opiate Dependence Support Group on Drugs.com.
Finished: Know Your Naloxone: Save a Life
- Surgeon General’s Advisory on Naloxone and Opioid Overdose. US Dept of Health and Human Services (HHS). April 5, 2018. Accessed April 5, 2018 at https://www.surgeongeneral.gov/priorities/opioid-overdose-prevention/naloxone-advisory.html
- Centers for Disease Control and Prevention (CDC). CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. Recommendations and Reports / March 18, 2016 / 65(1);1–49. Accessed March 29, 2018 at https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm
- Centers for Disease Control and Prevention (CDC). Injury Prevention & Control: Opioid Overdose. Data Overview. Accessed March 29, 2018 at https://www.cdc.gov/drugoverdose/data/index.html
- Evzio Instructions for Use. Drugs.com. Accessed March 29, 2018 at https://www.drugs.com/pro/evzio.html#ABIFU
- Evzio Prescribing Information. Accessed March 29, 2018 at http://www.evzio.com/pdfs/Evzio PI.PDF
- Blank C. First nasal spray helps with drug overdoses. Formulary Watch. November 20, 2015. Accessed March 29, 2018 at http://formularyjournal.modernmedicine.com/formulary-journal/news/first-nasal-spray-helps-drug-overdoses
- Narcan Nasal Spray. Manufacturers website. Accessed March 29, 2018 at http://www.narcannasalspray.com/how-to-get-nns/consumer-access/
- National Institute on Drug Abuse. Opioid Overdose Reversal with Naloxone (Narcan, Evzio). January 2018, Accessed April 5, 2018 at https://www.drugabuse.gov/related-topics/opioid-overdosereversal-naloxone-narcan-evzio.
- Narcan Nasal Spray Prescribing Information. Accessed Accessed March 29, 2018 at http://www.narcannasalspray.com/pdf/NARCAN-Prescribing-Information.pdf
- The Network for Public Health Law. Legal Interventions to Reduce Overdose Mortality: Naloxone Access and Overdose Good Samaritan Laws. Accessed March 29, 2018 at https://www.networkforphl.org/_asset/qz5pvn/legal-interventions-to-reduce-overdose.pdf